Melatonin (MT) is secreted by the pineal gland (PG) almost exclusively at night. Our previous work has shown that MT is present in humans and that its nocturnal secretion can be suppressed with bright artificial light (greater than 2000 lux). This effect of light is presumed to be mediated by neural pathways connecting the retina to the PG via the hypothalamus. At the hypothalamic level the effect of light is thought to be mediated by nicotinic cholinergic receptors. Suppression of MT is presently the only index of hypothalamic sensitivity to light. We have shown that humans have a high threshold for light-MT effects compared with experimental animals. Ordinary artificial light, for example, appears ineffective in humans. Abnormal hypothalamic sensitivity to light may be an important trait and pathogenic mechanism in manic-depressive illness, seasonal affective disorder and delayed sleep phase syndrome. The purpose of this project is (1) to standardize the light-MT suppression test (LMST), (2) to identify sources of variance in the LMST (age, sex, prior sleep or waking, prior exposure to light, etc.), and (3) to investigate hypothalamic sensitivity to light using the LMST in the disorders outlined above. We have standardized the administration of light by using high-intensity tungsten lamps. Spectral qualities are controlled by ultraviolet and infrared filters modifying the light projected into a ganzfeld dome, and intensities of light are varied by using neutral density filters. Blood samples are obtained before, during and after light administration. Using these methods a fluence-response curve for the LMST is being generated with the degree of MT suppression expressed as a function of log light intensity (watts/cm2).